Rheumatoid Arthritis Vaccine Candidate Suppresses Disease Progression in Mice
Novel vaccine modulates T cell responses in RA.
New data published in Vaccine shows that a rheumatoid arthritis (RA) vaccine candidate inhibited disease progression in animal models.
For the study, investigators sought to test the therapeutic efficacy of Ligand Epitope Antigen Presentation System (LEAPS) vaccines in 2 Th1 cell-drive mouse models of RA, cartilage proteoglycan induced arthritis (PGIA), and PG G1-domain-induced arthritis (GIA).
The DerG-PG70 (now designated CEL-4000) and J-PG70 vaccines were administered to the mice after onset of PGIA or GIA symptoms.
The results of the study showed that the DerG-PG70 vaccine inhibited disease progression in both PGIA and GIA, while the J-PG70 vaccine was ineffective.
In mice treated with DerG-PG70, splenic CD4+ cells were diminished in T helper (Th)1 and Th17 populations, but were abundant in Th2 and regulatory T cells.
In vitro spleen cell-secreted and serum cytokines from mice treated with DerG-PG70 showed a shift from a pro-inflammatory profile to an anti-inflammatory/regulatory profile. Furthermore, the DerG-PG70 peptide tetramers preferentially bound to CD4+ T cells of GIA spleen cells.
“Current treatments for RA focus on the alleviation of symptoms and delaying disease progression,” Dr Zimmerman, senior vice president of research, Cellular Immunology at CEL-SCI Corporation, said in a press release. “Our vaccination approach attempts to treat RA by impacting the pro-inflammatory immune response so that the body’s joints are no longer attacked by it.”
The DerG-PG70 vaccine exerts its therapeutic effect by interacting with CD4+ cells, resulting in an antigen-specific down-modulation of pathogenic T cell responses in both the PGIA and GIA models of RA, according to the authors.
“Based on these data and results from prior studies, we believe [DerG-PG70] could be a potentially valuable asset to the treatment of rheumatoid arthritis and it could be positioned as a first-line treatment to inhibit disease progression in newly diagnosed patients,” Geert Kersten, CEO of CEL-SCI, said in a release. “We are pleased to advance the development of [DerG-PG70] through the support of the National Institutes of Health (NIH) and look forward to advancing it into clinical trials in the future.”
The study was supported in part by funding of a phase 1 Small Business Innovation Research grant from the NIH’s National Institute of Arthritis Muscoskeletal and Skin Diseases, the release stated.